ProjectSummary The increased aggressiveness of melanoma in elderly patients leads to increased metastasis and therapyresistanceinthesepatients.Ourgoalinthisproposedresearchistounderstandthemolecular mechanisms underlying age-related increases in melanoma metastasis, as well as effects on the immune microenvironment. Our overall hypothesis is that aged patients have changes in the extracellular matrix (ECM) of the skin that leads to differential motility of melanoma and the immune cellsinthetumor. Totestthishypothesis,wewillundertaketwospecificaimsthatareoutlinedintheresearchproposal. The proposed studies are based on my findings from my previous studies that aging affects the metastasis in melanoma cells. My work identified various proteins that are de-regulated during aging, and our data showed a 35-fold decrease in levels of a collagen crosslinking protein, HAPLN1, during aging.Firstly,wewillassesstheeffectofcollagencrosslinkingmediatedbyHAPLN1onmediatingthe changes in migration of melanoma cells from the tumor. Secondly, we will focus on changes in the infiltration of lymphocytes into the tumor when age-related changes in HAPLN1 levels restructure the tumor ECM. We expect this research to generate targets for therapeutic implications in elderly melanomapatients. Apart from these goals, this NCI Predoctoral to Postdoctoral Fellow Transition Award will allow me to develop expertise in cancer research while providing me with funding to support my postdoctoral training. My training plan outlined in this proposal will take advantage of the extensive resources availabletomeatTheWistarInstituteandUniversityoftheSciencesintheF99phaseofmytraining. During this phase, my training will be overseen by my mentor, Dr. Ashani Weeraratna who has successfullymentoredseveralpostdoctoralandclinicalfellowsintheiracademiccareers.